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[Preprint]. 2020 May 28:2020.05.28.121640. [Version 1] doi: 10.1101/2020.05.28.121640

Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates

Jesse H Erasmus, Amit P Khandhar, Alexandra C Walls, Emily A Hemann, Megan A O’Connor, Patience Murapa, Jacob Archer, Shanna Leventhal, Jim Fuller, Thomas Lewis, Kevin E Draves, Samantha Randall, Kathryn A Guerriero, Malcolm S Duthie, Darrick Carter, Steven G Reed, David W Hawman, Heinz Feldmann, Michael Gale, David Veesler, Peter Berglund, Deborah Heydenburg Fuller
PMCID: PMC7265689  PMID: 32511417

Abstract

The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.

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